W(CO)5(L)-catalyzed endo-selective cyclization of allenyl silyl enol ethers: An efficient method for the cyclopentene annulation onto α,β-unsaturated ketones

Article abstract of DOI:10.1021/ol034365a

(Matrix presented) Indium-mediated allenylation of α,β -unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives 6-siloxy-1,2,5-trienes, which undergo W(CO) ₅(L)-catalyzed 5-endo cyclization to give the

Full text of DOI:10.1021/ol034365a

ORGANIC
LETTERS
2003
Vol. 5, No. 10
1725-1728
W(CO)5(L)-Catalyzed Endo-Selective
Cyclization of Allenyl Silyl Enol Ethers:
An Efficient Method for the
Cyclopentene Annulation onto
r,â-Unsaturated Ketones
Tomoya Miura,† Koichi Kiyota,† Hiroyuki Kusama,† Kooyeon Lee,‡
,‡
,†
Hyunseok Kim,‡ Sunggak Kim,§ Phil Ho Lee,* and Nobuharu Iwasawa*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku,
Tokyo 152-8551, Japan, Department of Chemistry, Kangwon National UniVersity,
Chunchon 200-701, Republic of Korea, and Center for Molecular Design and
Synthesis and Department of Chemistry, Korea AdVanced Institute of Science and
Technology, Daejeon 305-701, Republic of Korea
niwasawa@chem.titech.ac.jp; phlee@kangwon.ac.kr
Received March 1, 2003
ABSTRACT
Indium-mediated allenylation of r,â-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives 6-siloxy-
1,2,5-trienes, which undergo W(CO)5(L)-catalyzed 5-endo cyclization to give the corresponding cyclopentene derivatives in good yield. Furthermore,
this novel W(CO)5(L)-catalyzed cyclization of allenyl silyl enol ethers proceeds in a 6-endo manner when 5-siloxy-1,2,5-trienes are employed
as a substrate. In these reactions, effective electrophilic activation of allenyl compounds for attack by silyl enol ethers is achieved using a
catalytic amount of W(CO)6.
Allenyl compounds play an important role in synthetic
reactions due to their unique structure and high reactivity.1
Although π-allyl palladium(II) complex formation by the
carbopalladation of allenyl compounds with palladium(II)
compounds, followed by attack on the complex by nucleo-
philes, has been studied extensively (eq 1),2,3 simple transition
metal-catalyzed electrophilic activation of allenyl compounds
for attack by carbon nucleophiles has remained relatively
unexplored despite its high potential as a method for the
construction of carbon frameworks (eq 2).2,4-6
(3) For recent examples of the palladium-catalyzed carbocyclization of
allenyl compounds, see: (a) Ma, S.; Zhao, S. Org. Lett. 2000, 2, 2495-
2497. (b) Kang, S.-K.; Baik, T.-G.; Kulak, A. N.; Ha, Y.-H.; Lim, Y.; Park,
J. J. Am. Chem. Soc. 2000, 122, 11529-11530. (c) Shin, S.; RajanBabu,
T. V. J. Am. Chem. Soc. 2001, 123, 8416-8417. (d) Kang, S.-K.; Ha, Y.-
H.; Ko, B.-S.; Lim, Y.; Jung, J. Angew. Chem., Int. Ed. 2002, 41, 343-
345. (e) Franze´n, J.; Lo¨fstedt, J.; Dorange, I.; Ba¨ckvall, J.-E. J. Am. Chem.
Soc. 2002, 124, 11246-11247.
(4) For a review on the transition-metal catalyzed nucleophilic cyclization
of allenyl compounds, see: Bates, R. W.; Satcharoen, V. Chem. Soc. ReV.
2002, 31, 12-21.
(5) Transition metal-catalyzed cyclizations of allenyl compounds by
heteronucleophiles have been reported. For recent examples of 5-endo-
selective cyclization by oxygen nucleophiles, see: (a) Hashmi, A. S. K.;
Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 39,
2285-2288. (b) Hoffmann-Ro¨der, A.; Krause, N. Org. Lett. 2001, 3, 2537-
2538. (c) Ma, S.; Yu, Z. Angew. Chem., Int. Ed. 2002, 41, 1775-1778.
* Corresponding authors.
† Tokyo Institute of Technology.
‡ Kangwon National University.
§ Korea Advanced Institute of Science and Technology.
(1) (a) The Chemistry of Ketenes, Allenes, and Related Compounds; Patai,
S., Ed; John Wiley & Sons: New York, 1980; Part 1. (b) Schuster, H. F.;
Coppola, G. M. Allenes in Organic Synthesis; John Wiley & Sons: New
York, 1984.
(2) For a review on the palladium-catalyzed reaction of allenes, see:
Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. ReV. 2000,
100, 3067-3125.
10.1021/ol034365a CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/22/2003

Table 1. Indium-Mediated 1,4-Allenylsilylation of Cyclic
R,â-Unsaturated Ketones
We recently reported a concise method for cyclopentene
annulation onto R,â-unsaturated ketones utilizing indium-
mediated propargylation in the presence of tert-butyldi-
methylsilyl triflate and dimethyl sulfide, followed by
W(CO)5(thf)-catalyzed 5-endo-dig cyclization of the silyl
enol ether generated onto the terminal alkyne.7 One specific
feature of this reaction is that cyclopentene derivatives having
a double bond at the â,γ-position of the carbonyl group are
obtained selectively. We expected that by finding an ap-
propriate method for 1,4-allenylsilylation of R,â-unsaturated
ketones, followed by transition metal-catalyzed 5-endo
cyclization of the silyl enol ether generated onto the transition
metal-activated allenyl moiety, another useful cyclopentene
annulation could be achieved where the double bond of the
product is situated at the γ,δ-position of the carbonyl group.
Thus, these two procedures would constitute complementary
methods for cyclopentene annulation with control of double
bond position (Figure 1).
ketones when propargyl bromides having a substituent on
the terminal alkyne were employed.
We next examined the cyclization reaction using the
6-siloxy-1,2,5-trienes generated as a substrate. When 2a
was treated with an equimolar amount of preformed
W(CO)5(thf) in the presence of 3 molar equiv of H2O, 2a
was completely consumed at room temperature within 3 days
to give the 5-endo-cyclized ketone 3a as a single product in
71% yield. Furthermore, the reaction time was greatly
diminished (4 h) by carrying out the reaction with an
equimolar amount of W(CO)6 under direct photoirradiation
at 40 °C to give the same product 3a in 94% yield.10 This
reaction could be carried out successfully even with a
catalytic amount (as little as 10 mol %) of W(CO)6 under
Figure 1. Cyclopentene Annulation onto Cyclic R,â-Unsaturated
Ketones.
In the first place, allenylation in the presence of silyl triflate
and dimethyl sulfide was examined.8 As it is known that
indium reagents prepared from propargyl bromides having
a substituent on the terminal alkyne react with aldehydes or
ketones to give allenyl compounds as the major product,9
we expected that 1,4-allenylsilylation could be achieved by
employing indium reagents prepared from substituted pro-
pargyl bromides and indium metal.
Thus, to a THF solution of 2-methylcyclohex-2-en-1-one
1a were added in succession tert-butyldimethylsilyl triflate
and dimethyl sulfide to afford in situ 3-tert-butyldimethyl-
siloxycyclohex-2-enylsulfonium salt A, which was treated
at -78 °C with the indium reagent prepared from 1-bromo-
2-butyne and indium metal. The mixture was slowly warmed
to room temperature overnight to give the desired allenylated
silyl enol ether 2a in 77% yield. As summarized in Table 1,
the present preparative method was found to be generally
applicable to 1,4-allenylsilylation of cyclic R,â-unsaturated
(6) For recent examples of 5-endo-selective cyclization by nitrogen
nucleophiles, see: (a) Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Osawa, E.;
Yamaoka, Y.; Fujii, N.; Ibuka, T. J. Org. Chem. 1999, 64, 2992-2993. (b)
Rutjes, F. P. J. T.; Tjen, K. C. M. F.; Wolf, L. B.; Karstens, W. F. J.;
Schoemaker, H. E.; Hiemstra, H. Org. Lett. 1999, 1, 717-720.
(7) Iwasawa, N.; Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.; Lee, P. H.
Org. Lett. 2002, 4, 4463-4466.
(8) For another example of 1,4-addition with indium reagents in the
presence of t-butyldimethylsilyl triflate and dimethyl sulfide, see: Lee, P.
H.; Lee, K.; Kim, S. Org. Lett. 2001, 3, 3205-3207.
(9) For an example of In-mediated propargylation or allenylation, see:
(a) Isaac, M. B.; Chan, T.-H. J. Chem. Soc., Chem. Commun. 1995, 1003-
1004. (b) Yi, X.-H.; Meng, Y.; Hua, X.-G.; Li, C.-J. J. Org. Chem. 1998,
63, 7472-7480. (c) Nair, V.; Jayan, C. N.; Ros, S. Tetrahedron 2001, 57,
9453-9459. (d) Lee, K.; Seomoon, D.; Lee, P. H. Angew. Chem., Int. Ed.
2002, 41, 3901-3903.
(10) It is known that photoirradiation enhances ligand substitution on
the W(CO)5(L) complex; see: Kirtley, S. W. ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds; Pergamon
Press: Oxford, UK, 1982; Vol. 3, pp 1079-1148.
1726
Org. Lett., Vol. 5, No. 10, 2003

photoirradiation to give 3a in 69% yield. Other metal
complexes such as Pd(OAc)2, PdCl2, and PtCl2, failed to give
better results.11 When 2c was reacted in the presence of 3
molar equiv of D2O instead of H2O, the degree of deuterium
incorporation at the olefinic proton of 3c was more than
90%.12 On the basis of these results, the reaction is assumed
to proceed as follows: treatment of 2a with W(CO)6 under
photoirradiation would give the allene-W(CO)5 η2 complex
B. Next, intramolecular attack of the silyl enol ether occurs
on the distal carbon of the allene moiety to give the
vinylmetallic intermediate C. Finally, the carbon-tungsten
bond is protonated to give the 5-endo-cyclized ketone 3a,
with regeneration of the W(CO)5(thf) (Scheme 1).
cyclized ketone 3b in good yield. Varying the substituent
on the allene moiety (2c-e) did not lower the yield. Thus,
this 5-endo-trig cyclization of 6-siloxy-1,2,5-trienes consti-
tutes another useful method for cyclopentene annulation onto
R,â-unsaturated ketones utilizing a novel W(CO)5(L)-
catalyzed electrophilic activation of the allene moiety toward
attack by neutral carbon nucleophiles.
The following two reactions clearly demonstrate the
synthetic utility of these protocols. Thus, starting from
isomeric propargyl bromides, that is, 1-bromo-2-butyne and
3-bromo-1-butyne, either 6-siloxy-1,2,5-triene 2a or 6-siloxy-
5-en-1-yne 4 could be synthesized selectively, and subsequent
W(CO)5(L)-catalyzed reaction gave either regioisomer of the
cyclopentene annulated products 3a or 5 with good to perfect
control of the position of the double bond (Scheme 2).13
Scheme 1
Scheme 2
We then examined the generality of this reaction employ-
ing a variety of 6-siloxy-1,2,5-trienes as summarized in Table
2. The five-membered substrate 2b also gave the 5-endo-
We next applied this novel reaction to other types of
allenyl silyl enol ethers. Thus, the reaction of 5-siloxy-1,2,5-
triene 6a with 10 mol % W(CO)6 under photoirradiation in
toluene proceeded smoothly to give the 6-endo cyclized
ketone 7a in good yield. The same type of 6-endo cyclization
reaction was found to proceed similarly with acyclic
substrates 6b and 6c, although an equimolar amount of
W(CO)6 was required to obtain a good yield of the products
7b and 7c (Scheme 3).
Table 2. Stoichiometric and Catalytic Endo-Selective
Cyclization of 6-Siloxy-1,2,5-trienesa
In conclusion, we have developed a novel method for the
cyclization of allenyl silyl enol ethers in an endo manner
Scheme 3
a General procedure: a THF solution of the substrate, W(CO)6, and 3
molar equiv of H2O was irradiated at ambient temperature for 4-20 hours.
Org. Lett., Vol. 5, No. 10, 2003
1727

using a catalytic amount of W(CO)6 and realized an efficient
method for cyclopentene annulation onto R,â-unsaturated
ketones. In this reaction, effective activation of the allene
moiety is achieved by complexation with W(CO)5, allowing
attack by neutral carbon nucleophiles. Further studies to
expand the utility of this reaction are in progress in our
laboratory.
Acknowledgment. This research was partly supported by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology of
Japan, Grant R02-2002-000-00046-0 of the Basic Research
Program of the Korea Science & Engineering Foundation,
and the CMDS at KAIST. T. M. has been granted a Research
Fellowship of the Japan Society for the Promotion of Science
for Young Scientists.
(11) Use of Pd(OAc)2 or PdCl2 did not give 3a at all. When PtCl2 was
employed, a low yield of 3a was obtained along with a complex mixture
of unidentified products.
(12) Vinylmetallic intermediate underwent efficient deuteration at the
carbon-tungsten bond by means of D2O; see: Barluenga, J.; Ballesteros,
A.; Ru´a, R. B.; Santamar´ıa, J.; Rubio, E.; Toma´s, M. J. Am. Chem. Soc.
2003, 125, 1834-1842.
(13) While 3a was obtained as a single product, 5 was accompanied by
a small amount (about 10% of the product) of the olefinic regioisomer 3a.
The reason for the formation of this compound is not yet obvious.
Supporting Information Available: Preparative methods
and spectral and analytical data of compounds 2a-7c and
1H and 13C NMR spectra for compounds 2a and 3a. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL034365A
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Org. Lett., Vol. 5, No. 10, 2003